{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZBTB1, a zinc finger and BTB domain-containing transcriptional regulator, is critical for normal lymphoid development. Early studies using chemically induced mutations and transgenic mouse models revealed that disruption of ZBTB1 impairs T cell development at early thymic stages, while also affecting B and NK cell differentiation under competitive conditions. These findings underscore the essential role of ZBTB1 in establishing a robust lymphoid compartment through its transcriptional regulatory functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its function in lineage specification, ZBTB1 plays a pivotal role in maintaining genomic integrity during the replication of immune progenitors. Studies have demonstrated that in the absence of ZBTB1, cells show heightened sensitivity to replication stress, resulting in increased DNA damage and triggering p53-mediated apoptosis. This mechanism not only affects lymphoid cells but also impacts myeloid progenitors in competitive bone marrow environments, revealing that ZBTB1 is indispensable for protecting proliferating immune cells from replication-associated damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, ZBTB1 expression in lymphoid-primed multipotent progenitors prevents the activation of a default myeloid differentiation program, thereby ensuring proper lymphoid lineage commitment. Complementing its developmental functions, recent investigations in a T-cell lymphoma model using CRISPR-Cas9-mediated deletion in an EL4 cell line revealed that loss of ZBTB1 alters the expression profiles of numerous regulatory non-coding RNAs, including microRNAs and circular RNAs. These findings suggest that, in addition to its well-established role in normal hematopoiesis, ZBTB1 may also represent a potential molecular target for therapeutic intervention in lymphoid malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Owen M Siggs, Xiaohong Li, Yu Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZBTB1 is a determinant of lymphoid development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20112084"}], "href": "https://doi.org/10.1084/jem.20112084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22201126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22201126"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Divya Punwani, Karen Simon, Youngnim Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor zinc finger and BTB domain 1 is essential for lymphocyte development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1200623"}], "href": "https://doi.org/10.4049/jimmunol.1200623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22753936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22753936"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xin Cao, Ying Lu, Xianyu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zbtb1 Safeguards Genome Integrity and Prevents p53-Mediated Apoptosis in Proliferating Lymphoid Progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1600013"}], "href": "https://doi.org/10.4049/jimmunol.1600013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27402700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27402700"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xianyu Zhang, Ying Lu, Xin Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zbtb1 prevents default myeloid differentiation of lymphoid-primed multipotent progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.11356"}], "href": "https://doi.org/10.18632/oncotarget.11356"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27542215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27542215"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jun-Hong Wang, Chun-Wei Shi, Yi-Yuan Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA and circRNA Expression Analysis in a Zbtb1 Gene Knockout Monoclonal EL4 Cell Line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Infect Microbiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcimb.2021.706919"}], "href": "https://doi.org/10.3389/fcimb.2021.706919"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34290994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34290994"}]}]}]}